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1. 发明申请

WO2022198335A1 CYSTEINE ENGINEERED ANTIBODY CONSTRUCTS, CONJUGATES AND METHODS OF USE 审中-公开
公开(公告)号：WO2022198335A1
公开(公告)日：2022-09-29
申请号：PCT/CA2022/050453
申请日：2022-03-25
申请人： ZYMEWORKS INC.
发明人： RICH, James R. , SANCHES, Mario , DAS, Samir , FARBER, Patrick
IPC分类号： C07K16/00 , A61K47/68 , A61K49/00 , C07K16/30 , C07K16/46 , C12N15/13
摘要： Antibody constructs engineered to introduce at least one cysteine insertion mutation ("cysteine engineered antibody constructs") are described. The inserted cysteine residue(s) may be used as a site for conjugation of one or more active agents to the antibody construct to provide conjugates, such as antibody-drug conjugates.

2. 发明申请

WO2015077891A1 BISPECIFIC ANTIGEN-BINDING CONSTRUCTS TARGETING HER2 审中-公开
标题翻译： BISPECIFIC抗原结合治疗HER2
公开(公告)号：WO2015077891A1
公开(公告)日：2015-06-04
申请号：PCT/CA2014/051140
申请日：2014-11-27
申请人： ZYMEWORKS INC.
发明人： WEISSER, Nina E. , NG, Gordon Yiu Kon , WICKMAN, Grant Raymond , DIXIT, Surjit Bhimarao , ESCOBAR-CABRERA, Eric , SANCHES, Mario
IPC分类号： C07K16/46 , A61K39/395 , A61K47/48 , A61P35/00 , C07K16/28 , C12N15/13 , C12N5/10 , C40B40/08
CPC分类号： C07K16/32 , A61K39/39558 , A61K45/06 , A61K47/6803 , A61K47/6851 , A61K47/6855 , A61K47/6869 , A61K2039/505 , C07K16/3015 , C07K16/3069 , C07K2317/24 , C07K2317/31 , C07K2317/35 , C07K2317/41 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/55 , C07K2317/622 , C07K2317/73 , C07K2317/732 , C07K2317/77 , C07K2317/92 , C07K2317/94 , G01N33/57492
摘要： Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.
摘要翻译：本文提供了特异性结合HER2的二互补位的抗原结合构建体。双互补位抗原结合构建体包含结合HER2的ECD2的一个抗原结合部分，其结合HER2的ECD4的第二抗原结合部分和Fc结合部分。至少一个抗原结合部分是scFv。双互补位抗原结合构建体可用于治疗癌症。

3. 发明申请

WO2017059551A1 ANTIGEN-BINDING POLYPEPTIDE CONSTRUCTS COMPRISING KAPPA AND LAMBDA LIGHT CHAINS AND USES THEREOF 审中-公开
标题翻译：包含KAPPA和LAMBDA光链的抗原结合多肽构建体及其用途
公开(公告)号：WO2017059551A1
公开(公告)日：2017-04-13
申请号：PCT/CA2016/051183
申请日：2016-10-07
申请人： ZYMEWORKS INC.
发明人： UROSEV, Dunja , SANCHES, Mario , TOM-YEW, Stacey A.L. , PRESTA, Leonard G.
IPC分类号： C07K16/46 , A61K39/395 , C07K16/00 , C12N15/13 , C12N15/63 , C12P21/00
CPC分类号： C07K16/46 , C07K16/244 , C07K16/32 , C07K16/468 , C07K2299/00 , C07K2317/21 , C07K2317/31 , C07K2317/515 , C07K2317/55 , C07K2317/90 , C07K2317/92 , C07K2317/94 , C12N15/63 , C12P21/00
摘要： Provided herein are multispecific antigen-binding polypeptide constructs comprising at least two different heterodimers, each comprising a heavy chain and a light chain. At least one heterodimer comprises a Fab region comprising a lambda light chain and at least one heterodimer comprises a Fab region comprising a kappa light chain. One or more of the immunoglobulin heavy and light chains that form the antigen-binding polypeptide construct comprise amino acid modifications that promote correct pairing between the heavy and light chains to form the desired multispecific antigen-binding polypeptide construct. The amino acid modifications may be in the C H1 and/or C L domains, in the V H and/or V L domains, or a combination thereof.
摘要翻译：本文提供了包含至少两种不同异源二聚体的多特异性抗原结合多肽构建体，每个异二聚体包含重链和轻链。至少一个异源二聚体包含包含λ轻链的Fab区，并且至少一个异源二聚体包含包含κ轻链的Fab区。形成抗原结合多肽构建体的一个或多个免疫球蛋白重链和轻链包含促进重链和轻链之间的正确配对以形成所需多特异性抗原结合多肽构建体的氨基酸修饰。氨基酸修饰可以在CH1和/或CL结构域，VH和/或VL结构域中，或其组合中。

4. 发明申请

WO2015181805A1 MODIFIED ANTIGEN BINDING POLYPEPTIDE CONSTRUCTS AND USES THEREOF 审中-公开
标题翻译：改性抗体结合多肽构建体及其用途
公开(公告)号：WO2015181805A1
公开(公告)日：2015-12-03
申请号：PCT/IB2015/054107
申请日：2015-05-29
申请人： ZYMEWORKS INC.
发明人： SANCHES, Mario , SPRETER VON KREUDENSTEIN, Thomas
IPC分类号： C07K16/46 , A61K39/395 , C07K16/00 , C12N15/13
CPC分类号： C07K16/468 , C07K16/2863 , C07K16/32 , C07K16/36 , C07K2317/24 , C07K2317/31 , C07K2317/515 , C07K2317/522 , C07K2317/55 , C07K2317/92 , C07K2317/94
摘要： The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the CH1 and/or CL domains, one or more amino acid modifications in the VH and/or VL domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer typically preferentially pairs with the second light chain rather than first.
摘要翻译：本发明提供了可以包含第一异二聚体和第二异二聚体的异二聚体对，其中每个异二聚体包含免疫球蛋白重链或其片段和免疫球蛋白轻链或其片段。至少一个异源二聚体可以包含CH1和/或CL结构域中的一个或多个氨基酸修饰，VH和/或VL结构域中的一个或多个氨基酸修饰，或其组合。修饰的氨基酸可以是轻链和重链之间的界面的一部分，并且通常被修饰以在每个重链和期望的轻链之间产生优先配对，使得当两条重链和两条轻链异源二聚体对在细胞中共表达，第一异源二聚体的重链优先与轻链之一而不是另一个重合。同样，第二异二聚体的重链通常优先与第二轻链配对，而不是首先。

5. 发明申请

WO2021068074A1 MODIFIED EXTRACELLULAR DOMAIN OF GRANULOCYTE COLONY-STIMULATING FACTOR RECEPTOR (G-CSFR) AND CYTOKINES BINDING SAME 审中-公开
公开(公告)号：WO2021068074A1
公开(公告)日：2021-04-15
申请号：PCT/CA2020/051352
申请日：2020-10-08
申请人： ZYMEWORKS INC. , PROVINCIAL HEALTH SERVICES AUTHORITY , UVIC INDUSTRY PARTNERSHIPS INC.
发明人： VOLKERS, Gesa , FULLER, Megan , BOULANGER, Martin J. , DIXIT, Surjit Bhimarao , NELSON, Brad , SANCHES, Mario , LOVELESS, Bianca
IPC分类号： C07K14/715 , A61K35/12 , A61K35/17 , A61P29/00 , A61P31/00 , A61P35/00 , A61P37/06 , C07K14/705 , C07K19/00 , C12N1/21 , C12N15/12 , C12N15/27 , C12N15/62 , C12N15/63 , C12N15/85 , C12N5/078 , C12N5/10 , C12P21/02
摘要： Described herein are methods and compositions for selective activation of cells using variant cytokine receptor and cytokine pairs, wherein the cytokine receptors comprise an extracellular domain (ECD) of granulocyte-colony stimulating factor receptor (G-CSFR). In certain embodiments, the methods and compositions described herein are useful for exclusive activation of cells for adoptive cell transfer therapy. Thus, included herein are methods of producing cells expressing variant receptors that are selectively activated by a cytokine that does not bind its native receptor. Also disclosed herein are methods of treating a subject in need thereof, comprising administering to the subject cells expressing an variant receptor comprising an extracellular domain of G-CSFR and co-administering a variant cytokine that activates the variant receptor.

6. 发明申请

WO2014012082A2 MULTIVALENT HETEROMULTIMER SCAFFOLD DESIGN AN CONSTRUCTS 审中-公开
标题翻译：多功能混合器设计建筑
公开(公告)号：WO2014012082A2
公开(公告)日：2014-01-16
申请号：PCT/US2013/050408
申请日：2013-07-12
申请人： ZYMEWORKS INC.
发明人： DIXIT, Surjit, Bhimarao , D'ANGELO, Igor Edmondo, Paolo , SANCHES, Mario , NG, Gordon Yiu Kon
IPC分类号： C07K14/76 , C07K16/00
CPC分类号： C07K14/765 , C07K14/485 , C07K14/605 , C07K14/76 , C07K16/00 , C07K16/2803 , C07K16/2809 , C07K16/283 , C07K16/2896 , C07K16/40 , C07K2317/35 , C07K2317/622 , C07K2317/76 , C07K2319/00 , C07K2319/31
摘要： Provided herein are multifunctional heteromultimer proteins. In specific embodiments is a heteromultimer comprising: at least two polypeptide constructs, each polypeptide construct comprising at least one cargo polypeptide attached to a transporter polypeptide, said transporter polypeptides derived from a monomeric native protein such that said monomeric constructs associate to form the heteromultimer and said transporter polypeptides associate to form a quasi-native structure of the monomeric native protein or analog thereof. These therapeutically novel molecules encompass heteromultimers comprising constructs that function as scaffolds for the conjugation or fusion of therapeutic molecular entities (cargo polypeptides) resulting in the creation of bispecific or multivalent molecular species. Provided herein is a method for creation of bispecific or multivalent molecular species.
摘要翻译：本文提供多功能异源多聚蛋白。在具体实施方案中是异源多聚体，其包含：至少两个多肽构建体，每个多肽构建体包含连接到转运蛋白多肽的至少一种货物多肽，所述转运蛋白多肽衍生自单体天然蛋白，使得所述单体构建体缔合形成异源多聚体，并且所述转运蛋白多肽缔合以形成单体天然蛋白或其类似物的准天然结构。这些治疗性新颖的分子包括异源多聚体，其包含用作结合或融合治疗性分子实体（货物多肽）的构架的构建体，导致产生双特异性或多价分子物质。本文提供了用于产生双特异性或多价分子物质的方法。

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